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March 22, 2012

New Genomic Test Spares Patients Chemotherapy With No Adverse Effect On Survival

by editor

Testing a breast cancer tumor for its genomic signature can help identify which patients will need adjuvant systemic therapy (additional chemotherapy) after surgery, and spare its use in those for whom it is not necessary, according to the results of a study to be presented to the 8th European Breast Cancer Conference (EBCC-8) today (Thursday). Dr. Sabine Linn, an Associate Professor of Medical Oncology at The Netherlands Cancer Institute, Amsterdam, The Netherlands, will say that this is the first study where such a test has been incorporated in decision-making about adjuvant systemic therapy, and that the results are promising.

Adjuvant chemotherapy is used in order to destroy any microscopic cancer cells that might still be present in the body after surgery. Although it is effective, the side effects can be distressing. "Based on our data, the use of the genomic test could lead to a reduction of nearly 30% in the use of adjuvant chemotherapy without compromising patient outcomes," Dr. Linn will say. "This percentage may vary somewhat due to different guidelines used in different countries. These findings are important both for quality of life and for cutting down unnecessary healthcare costs."

The researchers studied follow-up data from 427 patients with early breast cancer who had taken part in a study called RASTER (MicroarRAy prognoSTics in breast cancER). Their cancers had not yet spread to the lymph nodes (node-negative). By looking for a particular selection of 70 genes in a tumor, the Mammaprint® test can predict which patients are at low and which at high risk of distant disease (metastasis); this enables doctors to select which patients could be spared the side effects of chemotherapy without adversely affecting their chances of disease-free survival. The study aimed to assess the feasibility of implementing the test in daily clinical practice in The Netherlands, as well as its effect on adjuvant systemic treatment decisions.

In addition to the results of the test, the researchers also used the risk—prediction tool Adjuvant!Online (AOL) in order to obtain a prognosis. AOL estimations were used retrospectively for comparison in the study because it is the most widely-used risk calculation tool. In around 35% of the patients the results of the two tests were discordant. The AOL risk estimates were not used at the time of treatment decision-making, which was based on the result of the Mammaprint® test, Dutch national guidelines and patients' and doctors' preferences.

In the group classified as low risk by the Mammaprint® test only 15% of the 219 patients received adjuvant chemotherapy as opposed to 81% (169/208) in the group classified as high risk by the Mammaprint® test. The first group had a five-year distant disease-free survival (DDFS) rate of 96% compared with 90% in the high risk group. In the groups where the Mammaprint® and AOL results were discordant, where the genomic test predicted a low risk and AOL a high risk, 43% of patients received endocrine therapy and 24% chemotherapy. There was a 98% DDFS in this group. Where AOL predicted a low risk but Mammaprint® a high one, 78% received endocrine therapy and 57% chemotherapy. The DDFS in this group was 95%.

"It is encouraging to be able to tell patients that we believe they will have just as good a chance of avoiding the recurrence of cancer by not having adjuvant chemotherapy as by having it," says Dr. Linn. "Many patients dread the idea of chemotherapy, and by avoiding it they can substantially reduce the stress involved in having cancer, as well as improve their overall quality of life."

Initially the test had to be carried out on fresh frozen tumor tissue, which involved complicated and expensive logistics. But since January, technical advances have meant that it is now possible to use formalin-fixed, paraffin-embedded tissue, the standard way to store tumor tissue, and this will enhance the availability of the test considerably. The researchers now intend to study two further genomic tests to see whether they can further refine prognosis in the same group of breast cancer patients.

"We will also assess further the cost-effectiveness of the 70-gene signature in comparison with the standard guidelines used to decide whether or not to give adjuvant chemotherapy. We believe that our results already show that the use of genomic tests is feasible and effective in clinical practice, and can help in decision-making," Dr. Linn will conclude.

Professor David Cameron, from the University of Edinburgh (Edinburgh, UK) and chair of EBCC-8 said: "There is great interest in being able to tell a woman that she does not need chemotherapy because her chances of surviving breast cancer are not improved by being given it. There are several potential tests to help clinicians and patients make this decision, and the one discussed here has always looked promising, but previously needed a snap frozen tumor sample which was not available for every patient. That this is no longer necessary is an important step forward for patients."